Research and Reference

MSM combo is a blend of bioavailable optiMSM, wholefood powders, vitamin C, magnesium and other co-factor nutrients to optimise sulfation, collagen synthesis and features numerous health benefits.
Methylsulfonylmethane (MSM), a sulfur-donor, will increase intracellular inorganic sulfate levels and contributeto the sulfation of glycosaminoglycans in the glycocalyx, therefore exhibiting antimicrobial and immunemodulating properties[1-3]. A well-sulfated, intact epithelial and endothelial glycocalyx, contribute to pathogenevasion and barrier functions, the regulation of inflammation, vascular permeability and tone, coagulation, themediation of shear stress[4, 5], lipid metabolism[6, 7], immune modulation and leukocyte adhesion[8-10], as wellas protection against oxidative stress[4]. Therefore, any changes in the degree of sulfation due to reducedavailability of inorganic sulfate, are associated with a wide range of pathophysiological consequences, such ascapillary leak syndrome and consequent oedema formation11, accelerated inflammation, hypercoagulation,platelet hyperaggregation, and loss of vascular responsiveness[5, 6].
Furthermore, as a source of organic sulfur, MSM will increase the synthesis of other sulfur amino acids andglutathione[12], apart from inorganic sulfate[2, 3]. It was shown that MSM attenuated paraquat-inducedpulmonary and hepatic injury in mice, confirmed by the reduction of inflammatory markers and the increase insuperoxide dismutase, glutathione, and catalase levels in lung and liver tissues[12]. Several research studiesdemonstrated that MSM inhibits lipopolysaccharide-induced release of oxidative stress biomarkers, such as nitricoxide and prostaglandin E2 in macrophages, through downregulation of NF-κB signaling[13, 14]. It has beenestablished that MSM potentially inhibits the translocation of the p65 subunit of NF-κB to the nucleus, therebyminimising downstream events associated with local and systemic inflammation[15-17]. Indeed, it has beendemonstrated that supplementation with MSM will minimise the expression of many pro-inflammatorycytokines[12, 15, 17]. MSM attenuated experimental colitis by reducing IL-1b levels and protected against hepaticliver injury by decreasing TNFα and IL-6 levels[12, 18]. In another study, MSM significantly mitigated lung andpancreatic histopathological changes, decreased serum amylase and myeloperoxidase activity, and inhibitedcaerulein-induced IL-1b expression[16].
The availability of inorganic sulfate for glycosaminoglycan sulfation has been associated with the developmentof many inflammatory diseases19, such as atherosclerosis, stroke, sepsis, diabetes mellitus and related renaldiseases, cardiovascular diseases, hypertension, obesity, pulmonary diseases, and various cancers4, 8, 20-27.MSM suppresses hepatic tumour development through activation of apoptosis and breast cancer growth bydown-regulating STAT3 and STAT5b pathways14, 28.
MSM is entirely safe and effective, taken at daily dosages of up to 4 g to prevent and treat inflammatorydiseases1.

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1. Butawan M, Benjamin R, Bloomer R. Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients. 2017;9(3):290. doi:10.3390/nu9030290

2. Nimni ME, Han B, Cordoba F. Are we getting enough sulfur in our diet? Nutr Metab (Lond). Nov 2007;4:24. doi:10.1186/1743-7075-4-24

3. Amadi B, Fagbemi AO, Kelly P, et al. Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus. Am J Clin Nutr. 2009;89(2):592-600. doi:10.3945/ajcn.2008.27092

4. Aldecoa C, Llau JV, Nuvials X, Artigas A. Role of albumin in the preservation of endothelial glycocalyx integrity and the microcirculation: a review. Annals of Intensive Care. Jun 22 2020;10(85):1-12. doi:10.1186/s13613-020-00697-1

5. Meli I. Assessing the role of albumin in the formation of the endothelial glycocalyx layer using a microfluidic in vitro model. University of Bern; 2019. https://www.cvrc.unibe.ch/e286839/e780601/20190201_MasterThesisIvoMeli.pdf

6. Kolarova H, Ambruzova B, Sindlerova LS, Klinke A, Kubala L. Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediators Inflamm. 2014;2014694312. doi:10.1155/2014/694312

7. Stopschinski BE, Holmes BB, Miller GM, et al. Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus α-synuclein and β-amyloid aggregates. J Biol Chem. 2018;293(27):10826-10840. doi:10.1074/jbc.ra117.000378

8. Hayden MR. Endothelial activation and dysfunction in metabolic syndrome, type 2 diabetes and coronavirus disease 2019. J Int Med Res. Jul 2020;48(7)0300060520939746. doi:10.1177/0300060520939746

9. Iba T, Levy JH. Derangement of the endothelial glycocalyx in sepsis. J Thromb Haemost. Feb 2019;17(2):283-294. doi:10.1111/jth.14371

10. Martin L, Koczera P, Zechendorf E, Schuerholz T. The endothelial glycocalyx: New diagnostic and therapeutic approaches in sepsis. Biomed Res Int. 2016;20163758278. doi:10.1155/2016/3758278

11. Arokiasamy S, King R, Boulaghrasse H, et al. Heparanase-dependent remodeling of initial lymphatic glycocalyx regulates tissue-fluid drainage during acute inflammation in vivo. Front Immunol. 2019;10:2316. doi:10.3389/fimmu.2019.02316

12. Amirshahrokhi K, Bohlooli S. Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice. Inflammation. Oct 2013;36(5):1111-1121. doi:10.1007/s10753-013-9645-8

13. Mohammadi S NM, Hamzeiy H, Maleki-Dizaji N, Pezeshkian M, Sadeghi-Bazargani H, Darabi M, Mostafalou S, Bohlooli S, Garjani A. Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats. . Adv Pharmacol Sci. 2012;2012:507278. doi:10.1155/2012/507278

14. Kim YH, Kim DH, Lim H, Baek D-Y, Shin H-K, Kim J-K. The Anti-inflammatory Effects of Methylsulfonylmethane on Lipopolysaccharide-Induced Inflammatory Responses in Murine Macrophages. Biol Pharm Bull. 2009;32(4):651-656. doi:10.1248/bpb.32.651

15. Kalman DS, Feldman S, Scheinberg AR, Krieger DR, Bloomer RJ. Influence of methylsulfonylmethane on markers of exercise recovery and performance in healthy men: a pilot study. J Int Soc Sports Nutr. Sep 27 2012;946. doi:10.1186/1550-2783-9-46

16. Velusamy RK, Tamizhselvi R. Protective effect of methylsulfonylmethane in caerulein-induced acute pancreatitis and associated lung injury in mice. J Pharm Pharmacol. Sep 2018;70(9):1188-1199. doi:10.1111/jphp.12946

17. van der Merwe M, Bloomer RJ. The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise. Journal of sports medicine (Hindawi Publishing Corporation). 2016 2016;2016:7498359-7498359.

18. Sousa-Lima I, Park SY, Chung M, et al. Methylsulfonylmethane (MSM), an organosulfur compound, is effective against obesity-induced metabolic disorders in mice. Metab Clin Exp. Oct 2016;65(10):1508-1521. doi:10.1016/j.metabol.2016.07.007

19. Martin, David, Michael. Oxidation of heparan sulphate by hypochlorite: role of N-chloro derivatives and dichloramine-dependent fragmentation. Biochem J. 2005;391(1):125-134. doi:10.1042/bj20050630

20. Dogne S, Flamion B, Caron N. Endothelial glycocalyx as a shield against diabetic vascular complications: Involvement of hyaluronan and hyaluronidases. Arterioscler Thromb Vasc Biol. Jul 2018;38(7):1427-1439. doi:10.1161/atvbaha.118.310839

21. Veraldi N, Zouggari N, de Agostini A. The challenge of modulating heparan sulfate turnover by multitarget heparin derivatives. Molecules. Jan 2020;25(2)390. doi:10.3390/molecules25020390

22. da Costa DS, Reis RL, Pashkuleva I. Sulfation of glycosaminoglycans and its implications in human health and disorders. Annu Rev Biomed Eng. 2017:1-26.

23. Reitsma S, Slaaf DW, Vink H, van Zandvoort M, Egbrink M. The endothelial glycocalyx: composition, functions, and visualization. Pflug Arch Eur J Physiol. Jun 2007;454(3):345-359. doi:10.1007/s00424-007-0212-8

24. Hayden MR. Type 2 diabetes mellitus increases the risk of late-onset Alzheimer’s disease: Ultrastructural remodeling of the neurovascular unit and diabetic gliopathy. Brain Sciences. 2019;9(10):262. doi:10.3390/brainsci9100262

25. Nadanaka S, Purunomo E, Takeda N, Tamura J, Kitagawa H. Heparan sulfate containing unsubstituted glucosamine residues: Biosynthesis and heparanase inhibitory activity. Glycobiology. Nov 2014;24(11):1206-1206.

26. Gordts P, Foley EM, Lawrence R, et al. Reducing macrophage proteoglycan sulfation increases atherosclerosis and obesity through enhanced Type I interferon signaling. Cell Metab. Nov 2014;20(5):813-826. doi:10.1016/j.cmet.2014.09.016

27. Simeonovic CJ, Popp SK, Starrs LM, et al. Loss of intra-islet heparan sulfate is a highly sensitive marker of type 1 diabetes progression in humans. PLoS One. Feb 7 2018;13(2)e0191360. doi:10.1371/journal.pone.0191360

28. Lim EJ, Hong DY, Park JH, et al. Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating STAT3 and STAT5b Pathways. PLoS One. 2012;7(4):e33361. doi:10.1371/journal.pone.0033361